NM_000083.3(CLCN1):c.1616_1617del (p.Thr539fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001041972.7

Allele description [Variation Report for NM_000083.3(CLCN1):c.1616_1617del (p.Thr539fs)]

NM_000083.3(CLCN1):c.1616_1617del (p.Thr539fs)

Gene:

CLCN1:chloride voltage-gated channel 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_000083.3(CLCN1):c.1616_1617del (p.Thr539fs)

HGVS:

NC_000007.14:g.143341958CA[2]
NG_009815.2:g.30833CA[2]
NM_000083.3:c.1616_1617delMANE SELECT
NP_000074.3:p.Thr539fs
NC_000007.13:g.143039051CA[2]
NC_000007.13:g.143039051_143039052del
NG_009815.1:g.30833CA[2]
NM_000083.2:c.1616_1617del
NR_046453.2:n.1567CA[2]
p.Thr539Serfs*40

Protein change:

T539fs

Links:

dbSNP: rs1554438432

NCBI 1000 Genomes Browser:

rs1554438432

Molecular consequence:

NM_000083.3:c.1616_1617del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_046453.2:n.1567CA[2] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Congenital myotonia, autosomal recessive form
Synonyms:: Myotonia congenita autosomal recessive; Becker disease; Myotonia generalized; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009715; MedGen: C0751360; Orphanet: 614; OMIM: 255700

Name:: Congenital myotonia, autosomal dominant form (THD)
Synonyms:: Myotonia congenita autosomal dominant; Thomsen disease; Thomsen's disease
Identifiers:: MONDO: MONDO:0008055; MedGen: C2936781; Orphanet: 614; OMIM: 160800

Recent activity

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mitochondrial basic amino acids transporter [Polyodon spathula]
mitochondrial basic amino acids transporter [Polyodon spathula]
gi|2031881242|ref|XP_041132696.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001205626	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17932099, 22094069, 23739125, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001205626

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 15, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions.

Fialho D, Schorge S, Pucovska U, Davies NP, Labrum R, Haworth A, Stanley E, Sud R, Wakeling W, Davis MB, Kullmann DM, Hanna MG.

Brain. 2007 Dec;130(Pt 12):3265-74. Epub 2007 Oct 11.

PubMed [citation]

PMID:: 17932099

Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene.

Mazón MJ, Barros F, De la Peña P, Quesada JF, Escudero A, Cobo AM, Pascual-Pascual SI, Gutiérrez-Rivas E, Guillén E, Arpa J, Eraso P, Portillo F, Molano J.

Neuromuscul Disord. 2012 Mar;22(3):231-43. doi: 10.1016/j.nmd.2011.10.013. Epub 2011 Nov 16.

PubMed [citation]

PMID:: 22094069

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205626.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Thr539Serfs*40) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 447055). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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